Dr Pantin on the Evolving Treatment Paradigm in PNH

Jeremy M. Pantin, MD, clinical director, Adult Transplant and Cellular Therapy Program, TriStar Centennial Medical Center, bone marrow transplant physician, Sarah Cannon Research Institute, discusses the evolution of the paroxysmal nocturnal hemoglobinuria (PNH) treatment paradigm and administration considerations for current and emerging agents in this disease.

Although the first complement inhibitors to be used for patients with PNH are effective, they are also associated with high rates of breakthrough hemolysis, and patients’ hemoglobin levels may never return to normal after receiving these agents, Pantin explains. These unmet needs have prompted researchers to develop new therapies for patients with PNH, Pantin emphasizes.

In 2023, the FDA granted priority review to crovalimab for the treatment of patients with PNH. Pantin notes that crovalimab is not the first C5-directed monoclonal antibody to be introduced in the PNH field. Ravulizumab-cwvz (Ultomiris), another C5 inhibitor, was FDA approved in 2018 for adult patients with PNH. In 2021, this indication was expanded to include pediatric patients with this disease. Crovalimab and ravulizumab can both be administered subcutaneously through on-body delivery systems. Although ravulizumab can also be received intravenously, subcutaneous dosing of the agent is not approved for pediatric patients, according to Pantin.

Iptacopan (Fabhalta) is the first complement factor B inhibitor to receive FDA approval in 2023 for adult patients with PNH, Pantin says. One advantage of this agent is that it is administered orally, which means that patients do not have to receive treatment at an infusion center or give themselves subcutaneous injections, Pantin notes. Additionally, the oral availability of iptacopan may improve treatment compliance rates among patients with PNH, Pantin explains. Historically, treatment compliance has been difficult to attain in this disease, and patients often die from PNH because of noncompliance to complement inhibitor therapy, according to Pantin. As iptacopan usage increases, this agent may improve PNH treatment outcomes due to its novel mechanism of action and administration route, Pantin concludes.